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Tribbles-1 regulates hepatic lipogenesis through post-transcriptional regulation of C/EBPα

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE70848 | GEO | 2015/07/14

SECONDARY ACCESSION(S): PRJNA289677

REPOSITORIES: GEO

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Tribbles-1 regulates hepatic lipogenesis through post-transcriptional regulation of C/EBPα [array]

Project description:Comparison of gene expression in livers of either WT mice or mice with hepatic specific deletion of the gene Tribbles1. Animal groups were both Trib1 cKO mice homozygous for a floxed allele of Trib1. Mice aged 8-10 weeks were treated with adeno associated virus (AAV) encoding Cre recombinase (AAV_Cre) or no gene (AAV_null). The WT group is mice treated with AAV_Null, the liver-specific KO group treated with AAV_Cre. Gene expression data was then used in Ingenuity Pathway analysis to attempt to identify upstream transcription factors that might be responsible for the gene expression changes observed. All animals were 8-10 weeks of age, and all animals were homozygous for the floxed allele of Trib1. WT animals were treated with AAV_Null, Trib1 liver specific KO mice were treated with AAV_Cre. Mice were euthanized at 1-week post injection of AAV, and RNA collected from whole liver tissue.

2015-07-14 | E-GEOD-70846 | biostudies-arrayexpress

Tribbles-1 regulates hepatic lipogenesis through post-transcriptional regulation of C/EBPα [array]

2015-07-14 | GSE70846 | GEO

Tribbles-1 regulates hepatic lipogenesis through post-transcriptional regulation of C/EBPα [ChIP-Seq]

2015-07-14 | GSE70716 | GEO

Tribbles-1 regulates hepatic lipogenesis through post-transcriptional regulation of C/EBP? [ChIP-Seq]

Project description:We report ChIP-Seq data for C/EBPa in livers of mice with liver-specific KO (LSKO) of Trib1 as compared to WT controls, or in livers of mice overexpressing C/EBPa via adeno-associated virus (AAV) as compared to controls. 8-10 week old Trib1 flox/flox mice treated with AAV_Null (WT) or AAV_Cre (LSKO); 8-10 week old C57B/6 WT mice treated with AAV_Null or AAV_Cebpa.

2015-07-14 | E-GEOD-70716 | biostudies-arrayexpress

Tribbles-1 regulates hepatic lipogenesis through posttranscriptional regulation of C/EBP?.

Project description:Variants near the gene TRIB1 are significantly associated with several plasma lipid traits, circulating liver enzymes, and the development of coronary artery disease in humans; however, it is not clear how its protein product tribbles-1 regulates lipid metabolism. Here, we evaluated mice harboring a liver-specific deletion of Trib1 (Trib1_LSKO) to elucidate the role of tribbles-1 in mammalian hepatic lipid metabolism. These mice exhibited increased hepatic triglyceride (TG) content, lipogenic gene transcription, and de novo lipogenesis. Microarray analysis revealed altered transcription of genes that are downstream of the transcription factor C/EBP?, and Trib1_LSKO mice had increased hepatic C/EBP? protein. Hepatic overexpression of C/EBP? in WT mice phenocopied Trib1_LSKO livers, and hepatic knockout of Cebpa in Trib1_LSKO mice revealed that C/EBP? is required for the increased lipogenesis. Using ChIP-Seq, we found that Trib1_LSKO mice had increased DNA-bound C/EBP? near lipogenic genes and the Trib1 gene, which itself was transcriptionally upregulated by C/EBP? overexpression. Together, our results reveal that tribbles-1 regulates hepatic lipogenesis through posttranscriptional regulation of C/EBP?, which in turn transcriptionally upregulates Trib1. These data suggest an important role for C/EBP? in mediating the lipogenic effects of hepatic Trib1 deletion and provide insight into the association between TRIB1 and plasma lipids, and liver traits in humans.

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Energy stress-induced circEPB41(2) regulates lipogenesis through histone modifications

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-10-11 | GSE234825 | GEO

Regulation of gene expression through genome-wide co-binding of Hoxa9 and C/EBPα in transformed HSCs

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-06-11 | E-GEOD-58362 | biostudies-arrayexpress

Post-transcriptional Regulation of De Novo Lipogenesis by mTORC1-S6K1-SRPK2 Signaling.

Project description:mTORC1 is a signal integrator and master regulator of cellular anabolic processes linked to cell growth and survival. Here, we demonstrate that mTORC1 promotes lipid biogenesis via SRPK2, a key regulator of RNA-binding SR proteins. mTORC1-activated S6K1 phosphorylates SRPK2 at Ser494, which primes Ser497 phosphorylation by CK1. These phosphorylation events promote SRPK2 nuclear translocation and phosphorylation of SR proteins. Genome-wide transcriptome analysis reveals that lipid biosynthetic enzymes are among the downstream targets of mTORC1-SRPK2 signaling. Mechanistically, SRPK2 promotes SR protein binding to U1-70K to induce splicing of lipogenic pre-mRNAs. Inhibition of this signaling pathway leads to intron retention of lipogenic genes, which triggers nonsense-mediated mRNA decay. Genetic or pharmacological inhibition of SRPK2 blunts de novo lipid synthesis, thereby suppressing cell growth. These results thus reveal a novel role of mTORC1-SRPK2 signaling in post-transcriptional regulation of lipid metabolism and demonstrate that SRPK2 is a potential therapeutic target for mTORC1-driven metabolic disorders.

| S-EPMC5920692 | biostudies-literature

KRAS drives lung cancer metastasis through lncRNA-mediated transcriptional and post-transcriptional regulation

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-12-17 | GSE124631 | GEO

GRLD-1 regulates cell-wide abundance of glutamate receptor through post-transcriptional regulation.

Project description:AMPA receptors mediate most of the fast postsynaptic response at glutamatergic synapses. The abundance of AMPA receptors in neurons and at postsynaptic membranes is tightly regulated. It has been suggested that changes in synaptic AMPA receptor levels are an important regulatory event in synaptic plasticity and learning and memory. Although the local, synapse-specific regulation of AMPA receptors has been intensely studied, global, cell-wide control is less well understood. Using a forward genetic approach, we identified glutamate receptor level decreased-1 (GRLD-1), a putative RNA-binding protein that was required for efficient production of GLR-1 in the AVE interneurons in the nematode Caenorhabditis elegans. In grld-1 mutants, GLR-1 levels were markedly reduced. Consistently, glutamate-induced currents in AVE were diminished and glr-1-dependent nose-touch avoidance behavior was defective in grld-1 mutants. We propose that this evolutionarily conserved family of proteins controls the abundance of GLR-1 by regulating glr-1 transcript splicing.

| S-EPMC3087617 | biostudies-literature

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